Gabapentin (Neurontin®) is an anti-convulsant agent that is useful in the treatment of epilepsy and has recently been shown to be a potential treatment for neurogenic pain. It is 1-(aminomethyl)-cyclohexylacetic acid of structural formula:

Gabapentin is one of a series of compounds of formula
in which R is hydrogen or a lower alkyl radical and n is 4, 5, or 6. These compounds are described U.S. Pat. No. 4,024,175 and its divisional U.S. Pat. No. 4,087,544. Gabapentin is useful in the treatment of a number of diseases, including pain and epilepsy.
Gabapentin and related compounds, such as pregabalin, may be referred to as alpha-2-delta ligands. An alpha-2-delta receptor ligand is any molecule which binds to any sub-type of the human calcium channel alpha-2-delta subunit. The calcium channel alpha-2-delta subunit comprises a number of sub-types which have been described in the literature:    e.g. N. S. Gee, J. P. Brown, V. U. Dissanayake, J. Offord, R. Thurlow, and G. N. Woodruff, J-Biol-Chem 271 (10):5768-76, 1996, (type 1);    Gong, J. Hang, W. Kohler, Z. Li, and T-Z. Su, J. Membr. Biol. 184 (1):35-43, 2001, (types 2 and 3);    E. Marais, N. Klugbauer, and F. Hofmann, Mol. Pharmacol. 59 (5):1243-1248, 2001. (types 2 and 3); and    N. Qin, S. Yagel, M. L. Momplaisir, E. E. Codd, and M. R. D'Andrea. Mol. Pharmacol. 62 (3):485-496, 2002, (type 4). They may also be known as GABA analogs.
International Patent Applications Nos. WO0230871 and WO0222568 describe compounds of the type I and type II, respectively,

which also have affinity for the gabapentin binding site and have physiological activities similar to gabapentin, particularly with respect to analgesia.
International Patent Application No. WO0119817 describes 3-pyrrolidinyloxy-3′-pyridyl ether compounds which are useful for controlling neurotransmitter release.
International Patent Application No. WO0222575 describes benzamidine derivatives which are serine protease inhibitors.
Certain of the compounds embraced within the broadest formula of the present invention have been disclosed for utilities not connected with the present invention, in particular according to Table 1:
TABLE 1 RRefBnO—Acta Chem Scand, 1990, 243-51(2S,4S)-4-(benzyloxy)pyrrolidine-2-carboxylic acidBnS—Chem Pharm Bull, 1972, 543-49(2S,4S)-4-(benzylthio)pyrrolidine-2-J Med Chem, 1993, 1902-13carboxylic acidJOC, 1981, 4182-4187  (2S,4S)-4-phenoxypyrrolidine-2-carboxylic acidJ. Med Chem, 1988, 1148-60  (2S,4S)-4-(2-naphthyloxy)pyrrolidine-2- carboxylic acidJ Med Chem, 1988, 1148-60  (2S,4S)-4-[(4- methoxybenzyl)thio]pyrrolidine-2- carboxylic acidJOC, 1970, 1924-1927 J Med Chem, 1993, 1902-1912  (2S,4S)-4-[(4- methylphenyl)thio]pyrrolidine-2-carboxylic acidJ Med Chem, 1993, 1402-13  (2S,4S)-4-(phenylthio)pyrrolidine-2- carboxylic acidJ Med Chem, 1988, 1148-60  (2S,4S)-4-(2-naphthylthio)pyrrolidine-2- carboxylic acidJ Med Chem, 1988, 1148-60 Bn—J Med Chem, 1988, 1148-60(2S,4S)-4-benzylpyrrolidine-2-carboxylicJOC, 1995, 2925-30acid  (2S,4S)-4-(3-methoxybenzyl)pyrrolidine-2- carboxylic acidJOC, 1995, 2925-30  (2S,4S)-4-[4- (trifluoromethyl)benzyl]pyrrolidine-2- carboxylic acidJOC, 1995, 2925-30  (2S,4S)-4-[(4-nitrobenzyl)oxy]pyrrolidine-2- carboxylic acidJapanese Patent Application No. JP 04154731  (2S,4S)-4-[(4- cyclohexylbenzyl)thio]pyrrolidine-2- carboxylic acidJapanese Patent Application No. JP 10265456  (2S,4S)-4-(4-chlorobenzyl)pyrrolidine-2- carboxylic acidUK Patent Application No. GB 2078733  (2S,4S)-4-(4-fluorophenoxy)pyrrolidine-2- carboxylic acidU.S. Pat. No. 4,316,906  (2S,4S)-4-(4-methylphenoxy)pyrrolidine-2- carboxylic acidU.S. Pat. No. 4,316,906  (2S,4S)-4-(3- methylthiophenoxy)pyrrolidine-2-carboxylic acidU.S. Pat. No. 4,316,906  (2S,4S)-4-(4-chlorophenoxy)pyrrolidine-2- carboxylic acidU.S. Pat. No. 4,316,906  (2S,4S)-4-(4-methoxyphenoxy)pyrrolidine- 2-carboxylic acidU.S. Pat. No. 4,316,906  (2S,4S)-4-(1-naphthalenyloxy)pyrrolidine- 2-carboxylic acidU.S. Pat. No. 4,316,906  (2S,4S)-4-(4-chlorophenylthio)pyrrolidine- 2-carboxylic acidU.S. Pat. No. 4,316,906  (2S,4S)-4-(3- trifluoromethylphenylthio)pyrrolidine-2- carboxylic acidU.S. Pat. No. 4,316,906  (2S,4S)-4-(4-fluorophenylthio)pyrrolidine-2- carboxylic acidUK Patent Application No. GB 2028327  (2S,4S)-4-(4- acetyloxyphenylthio)pyrrolidine-2- carboxylic acidUK Patent Application No. GB 2028327  (2S,4S)-4-(4-chlorobenzyloxy)pyrrolidine- 2-carboxylic acidU.S. Pat. No. 4,311,705  (2S,4S)-4-(4-phenyl-phenoxy)pyrrolidine-2- carboxylic acidU.S. Pat. No. 4,311,705 (2S,4S)-4-(4-phenyl-phenylthio)pyrrolidine- 2-carboxylic acidU.S. Pat. No. 4,311,705  (2S,4S)-4-(4-methyl-benzyloxy)pyrrolidine- 2-carboxylic acidU.S. Pat. No. 4,462,943  (2S,4S)-4-(4-fluorobenzyl)pyrrolidine-2- carboxylic acidU.S. Pat. No. 4,462,943